Fighting the Huntington’s Disease with a G-Quadruplex-Forming Aptamer Specifically Binding to Mutant Huntingtin Protein: Biophysical Characterization,In Vitro and In Vivo Studies

A set of guanine-rich aptamers able to preferentially recognize full-length huntingtin with an expanded polyglutamine tract has been recently identified, showing high efficacy in modulating the functions of the mutated protein in a variety of cell experiments. We here report a detailed biophysical characterization of the best aptamer in the series, named MS3, proved to adopt a stable, parallel G-quadruplex structure and show high nuclease resistance in serum. Confocal microscopy experiments on HeLa and SH-SY5Y cells, as models of non-neuronal and neuronal cells, respectively, showed a rapid, dose-dependent uptake of fluorescein-labelled MS3, demonstrating its effective internalization, even in the absence of transfecting agents, with no general cytotoxicity. Then, using a well-established Drosophila melanogaster model for Huntington’s disease, which expresses the mutated form of human huntingtin, a significant improvement in the motor neuronal function in flies fed with MS3 was observed, proving the in vivo efficacy of this aptamer.     

Leptin Signaling in Obesity and Colorectal Cancer

Obesity and colorectal cancer (CRC) are among the leading diseases causing deaths in the world, showing a complex multifactorial pathology. Obesity is considered a risk factor in CRC development through inflammation, metabolic, and signaling processes. Leptin is one of the most important adipokines related to obesity and an important proinflammatory marker, mainly expressed in adipose tissue, with many genetic variation profiles, many related influencing factors, and various functions that have been ascribed but not yet fully understood and elucidated, the most important ones being related to energy metabolism, as well as endocrine and immune systems. Aberrant signaling and genetic variations of leptin are correlated with obesity and CRC, with the genetic causality showing both inherited and acquired events, in addition to lifestyle and environmental risk factors; these might also be related to specific pathogenic pathways at different time points. Moreover, mutation gain is a crucial factor enabling the genetic process of CRC. Currently, the inconsistent and insufficient data related to leptin’s relationship with obesity and CRC indicate the necessity of further related studies. This review summarizes the current knowledge on leptin genetics and its potential relationship with the main pathogenic pathways of obesity and CRC, in an attempt to understand the molecular mechanisms of these associations, in the context of inconsistent and contradictory data. The understanding of these mechanisms linking obesity and CRC could help to develop novel therapeutic targets and prevention strategies, resulting in a better prognosis and management of these diseases.     

Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR)

Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies.     

Efficient shape optimization for certain and uncertain aerodynamic design

In this paper, we present novel developments in aerodynamic shape optimization based on shape calculus as well as the proper treatment of aleatoric uncertainties in the field of aerodynamic design.     

Three-dimensional segmentation and growth-rate estimation of small pulmonary nodules in helical CT images

Small pulmonary nodules are a common radiographic finding that presents an important diagnostic challenge in contemporary medicine. While pulmonary nodules are the major radiographic indicator of lung cancer, they may also be signs of a variety of benign conditions. Measurement of nodule growth rate over time has been shown to be the most promising tool in distinguishing malignant from nonmalignant pulmonary nodules. In this paper, we describe three-dimensional (3-D) methods for the segmentation, analysis, and characterization of small pulmonary nodules imaged using computed tomography (CT). Methods for the isotropic resampling of anisotropic CT data are discussed. 3-D intensity and morphology-based segmentation algorithms are discussed for several classes of nodules. New models and methods for volumetric growth characterization based on longitudinal CT studies are developed. The results of segmentation and growth characterization methods based on in vivo studies are described. The methods presented are promising in their ability to distinguish malignant from nonmalignant pulmonary nodules and represent the first such system in clinical use.     

Controlled Growth of ZnO Nanowires and Their Optical Properties

This article surveys recent developments in the rational synthesis of single‐crystalline zinc oxide nanowires and their unique optical properties. The growth of ZnO nanowires was carried out in a simple chemical vapor transport and condensation (CVTC) system. Based on our fundamental understanding of the vapor–liquid–solid (VLS) nanowire growth mechanism, different levels of growth controls (including positional, orientational, diameter, and density control) have been achieved. Power‐dependent emission has been examined and lasing action was observed in these ZnO nanowires when the excitation intensity exceeds a threshold (∼40 kW cm^–2). These short‐wavelength nanolasers operate at room temperature and the areal density of these nanolasers on substrate readily reaches 1 × 10¹⁰ cm^–2. The observation of lasing action in these nanowire arrays without any fabricated mirrors indicates these single‐crystalline, well‐facetted nanowires can function as self‐contained optical resonance cavities. This argument is further supported by our recent near‐field scanning optical microscopy (NSOM) studies on single nanowires.     

Reliability enhancement with the aid of transient infrared thermal analysis of smart Power MOSFETs during short circuit operation

The usage of novel measurement techniques enhances the capabilities of researchers and power device manufacturers to understand and address reliability problems in novel Smart Power Devices. Along this line of argument, this work describes a method to improve the reliability of the smart Power MOSFET devices by design. The design optimization process involves Silicon layout, interconnections, packaging and protection strategy as well. Accurate thermal transient analyses, made possible by the unique features of a custom infrared radiometric microscope experimental setup which allows dynamic temperature detection with a bandwidth of 1 MHz over the chip area, indicated the way to minimize peak temperature and to verify the effect of the optimization.